The capsular polysaccharide of Neisseria meningitidis group C (MCPS) is a homopolymer of alpha (2->9) linked sialic acid residues. The polysaccharide is a thymus independent (TI) which is poorly immunogenic in infants and young children. Our previous studies demonstrated that the immune response to MCPS in BALB/c mice provides a model system which closely parallels the response in man. In order to compare the response to MCPS-TT, a thymus dependent form of the antigen, we have generated two panels of monoclonal antibodies (mAb) from mice immunized with MCPS-TT and boosted with MCPS-TT (C2 Mab) or formalin fixed bacteria (CP mAb). The anti-MCPS Mab are primarily of the IgG3 (53%) and IgM (27%) isotypes, whereas the anti-C2 and anti-CP mAbs are mainly IgG1 (87% and 88% respectively). The data indicate a change in fine specificity as assessed on native MCPS and a naturally occurring non-o-acetylated form, OAc-. As reported earlier, the anti-MCPS mAb are predominantly of two specificities, MCPS specific (47%) or Oac- >> MCPS (20%). The anti-C2 mAb are more diverse, none are MCPS only specific, 27% are MCPS = Oac-, 20% are MCPS >Oac- and 20% are Oac- >>. The anti-CP mAb were more similar to the anti- C2 mAbs than the anti-MCPS mAbs suggesting that the secondary antibody repertoire is determined by the primary immunization. Moreover the data also suggest the anti-C2 and anti-CP mAbs are of higher avidity than the anti-MCPS Mabs. The [OD 2] (concentration of mAb that results in fluorescence unit = 2 on a scale of 0-4 in a direct binding ELISA) for the majority of the anti-C2 and anti-CP mAbs are 10-100 fold lower than the [OD 2] for most of the anti-MCPS mAbs. To examine differences in affinity maturation between the TI and TD form of MCPS, we are currently establishing methods to measure intrinsic affinity constants. We will also test the IgG1 anti-C2 and anti-CP mAbs for bactericidal activity using mouse complement.